Objectives Dendritic cells play a pivotal role in the initiation of innate and adaptive immune responses in host reaction to microbial infection as well as in autoimmune pathology. DC subsets in peripheral blood consist of myeloid DC 1 (MDC1), plasmocytoid DC (PDC), and myeloid DC2 (MDC2) that differ in their expression of Toll-like receptor repertoire and cytocine expression upon stimulation. Several inflammatory diseases have been reported to have altered DC subsets distribution such as Sjögren’s, Lupus erythematosus, Hepatitis and HIV Infection. Little data exist about the impact of TNF-blocking agents on peripheral blood DC subsets.
Methods 38 patients with active rheumatic disease (16 rheumatoid arthritis (RA), 14 spondylarthritis (SPA), 8 psoriatic arthritis (PSA)) requiring TNF-blocking therapy due to insuffient disease control under DMARD therapy were prospectively followed for 12 weeks after initiation of etanercept treatment (timepoints: 0,week 2, 6,and 12). Peripheral blood dc subsets were evaluated by flow cytometry using the different expression of BDCA antigens (Milthenyi KIT). Prednisolon dose was <10mg and the individual Prednisolon dose was not altered during the observation period. A historic group of 29 healthy individuals served as controls.
Results Independent from the underlying rheumatic disease all patients showed significantly reduced numbers of peripheral blood MDC1 prior to initiation of Etanercept therapy. The numbers of MDC1 negatively correlated with values of CRP (CC -0,36, p<0,05).
MDC2 were significantly reduced in patients with rheumatoid arthritis but not in patients with spondylarthritis or psoriatic arthritis. MDC2 where reduced in RA patients and SPA patients but not in patients with PSA.
During Etanercept therapy numbers of MDC1 significantly increased within 2 weeks and further increased by week 12 (from 6791±747/ml to 16170±2327/ml). While PDC numbers showed the same pattern (from 5523±461/ml to 8329±935/m), the numbers of MDC2 were not significantly changed (1011±121/ml to 1352±219/ml). Parallel to the changes in MDC and PDC numbers Etanercept therapy induced a rapid decline in CRP-values (14,7mg/l±2,2 to 5,9mg/l+1,1) in DAS28 (from 4,14±0,45 to 2,48±0,31) and BASDAI (4,4±0,86 to 2,33±0,33) at week 2 (all data mean±SEM). By week 12 DAS28 and BASDAI had further declined.
Conclusions Active disease in rheumatoid arthritis, spondylarthritis or psoriatic arthritis is associated with reduced numbers of peripheral blood dendritic cells especially MDC1. This effect seems to be non-specifically related to the inflammatory response and independent of the type of rheumatic disease. MDC1 and PDC did not further decrease but increased during 12 week Etanercept therapy. Therefore the observed changes in peripheral blood DC subsets do not to contribute to the immunosuppressive effects of a TNF blocking therapy.
Disclosure of Interest R. Zeuner Grant/Research support from: Investigator originated study, that has been supported by a peer reviewed grant of Pfizer, K. Kay: None Declared, S. Boettcher: None Declared, J. Schroeder Speakers Bureau: Speakers fee’s from Pfizer & MSD